Šantak Maja, Örvell Claes, Gulija Tanja Košutić
Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, Zagreb 10 000, Croatia.
Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm 14 186, Sweden.
J Gen Virol. 2015 May;96(Pt 5):982-990. doi: 10.1099/vir.0.000059. Epub 2015 Jan 22.
In spite of the success of the mumps vaccination, recent mumps outbreaks have been reported even among individuals with a history of mumps vaccination. For a better understanding of why the vaccination failed in cases of vaccinees who fell ill during recent mumps outbreaks, the immunological events during infection and/or vaccination should be better defined. In the work presented here we sought to identify new neutralization sites on the mumps virus surface glycoproteins. By using anti-mumps mAbs, three amino acid positions at residues 221, 323 and 373 in the F protein of mumps virus were shown to be located in at least two conformational neutralization epitopes. mAbs that specifically target these sites effectively neutralized mumps virus in vitro. The newly acquired glycosylation site at position 373 or loss of the existing one at position 323 was identified as the mechanism behind the escape from the specific mAbs. Based on the findings of this study, we suggest that the influence of the antigenic structure of the F protein should not be ignored in a thorough investigation of the underlying mechanism of the mumps vaccine failure or when making a strategy for development of a new vaccine.
尽管腮腺炎疫苗接种取得了成功,但近期甚至在有腮腺炎疫苗接种史的个体中也报告了腮腺炎疫情。为了更好地理解在近期腮腺炎疫情中患病的疫苗接种者中疫苗为何失效,应更明确感染和/或接种疫苗期间的免疫事件。在本文所展示的研究中,我们试图确定腮腺炎病毒表面糖蛋白上新的中和位点。通过使用抗腮腺炎单克隆抗体,发现腮腺炎病毒F蛋白中第221、323和373位的三个氨基酸位置至少位于两个构象中和表位中。特异性靶向这些位点的单克隆抗体在体外能有效中和腮腺炎病毒。第373位新获得的糖基化位点或第323位现有糖基化位点的缺失被确定为逃避特异性单克隆抗体的机制。基于本研究的结果,我们建议,在全面调查腮腺炎疫苗失效的潜在机制或制定新疫苗开发策略时,不应忽视F蛋白抗原结构的影响。